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Cx3cr1 deficiency in mice attenuates hepatic granuloma formation during acute schistosomiasis by enhancing the M2-type polarization of macrophages.
- Source :
-
Disease models & mechanisms [Dis Model Mech] 2015 Jul 01; Vol. 8 (7), pp. 691-700. Date of Electronic Publication: 2015 Apr 21. - Publication Year :
- 2015
-
Abstract
- Acute schistosomiasis is characterized by pro-inflammatory responses against tissue- or organ-trapped parasite eggs along with granuloma formation. Here, we describe studies in Cx3cr1(-/-) mice and demonstrate the role of Cx3cr1 in the pathoetiology of granuloma formation during acute schistosomiasis. Mice deficient in Cx3cr1 were protected from granuloma formation and hepatic injury induced by Schistosoma japonicum eggs, as manifested by reduced body weight loss and attenuated hepatomegaly along with preserved liver function. Notably, S. japonicum infection induced high levels of hepatic Cx3cr1 expression, which was predominantly expressed by infiltrating macrophages. Loss of Cx3cr1 rendered macrophages preferentially towards M2 polarization, which then led to a characteristic switch of the host immune defense from a conventional Th1 to a typical Th2 response during acute schistosomiasis. This immune switch caused by Cx3cr1 deficiency was probably associated with enhanced STAT6/PPAR-γ signaling and increased expression of indoleamine 2,3-dioxygenase (IDO), an enzyme that promotes M2 polarization of macrophages. Taken together, our data provide evidence suggesting that CX3CR1 could be a viable therapeutic target for treatment of acute schistosomiasis.<br /> (© 2015. Published by The Company of Biologists Ltd.)
- Subjects :
- Acute Disease
Animals
Disease Models, Animal
Female
Granuloma etiology
Granuloma immunology
Granuloma pathology
Indoleamine-Pyrrole 2,3,-Dioxygenase metabolism
Liver Cirrhosis, Experimental etiology
Liver Cirrhosis, Experimental immunology
Liver Cirrhosis, Experimental pathology
Liver Diseases, Parasitic immunology
Liver Diseases, Parasitic pathology
Macrophages classification
Macrophages pathology
Mice
Mice, Inbred C57BL
Mice, Knockout
Ovum immunology
PPAR gamma metabolism
Receptors, Interleukin-8A genetics
STAT6 Transcription Factor metabolism
Schistosoma japonicum immunology
Schistosomiasis japonica complications
Signal Transduction
Th2 Cells immunology
Th2 Cells pathology
Liver Diseases, Parasitic etiology
Macrophages immunology
Receptors, Interleukin-8A deficiency
Schistosomiasis japonica immunology
Schistosomiasis japonica pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1754-8411
- Volume :
- 8
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- Disease models & mechanisms
- Publication Type :
- Academic Journal
- Accession number :
- 26035381
- Full Text :
- https://doi.org/10.1242/dmm.018242